评估谷胱甘肽S-转移酶基因多态性和诱变敏感性，作为先前诊断为早期头颈癌患者发生第二原发性肿瘤的风险因素。

Evaluation of glutathione S-transferase polymorphisms and mutagen sensitivity as risk factors for the development of second primary tumors in patients previously diagnosed with early-stage head and neck cancer.

作者信息

Minard Charles G, Spitz Margaret R, Wu Xifeng, Hong Waun Ki, Etzel Carol J

机构信息

Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.

出版信息

Cancer. 2006 Jun 15;106(12):2636-44. doi: 10.1002/cncr.21928.

DOI:10.1002/cncr.21928

PMID:16703596

Abstract

BACKGROUND

The objective of this study was to evaluate the effects of polymorphisms in 2 genes in the glutathione S-transferase (GST) family and the mutagen-sensitivity phenotype on the risk of second primary tumors (SPTs) in patients with previously diagnosed early-stage head and neck squamous cell carcinoma. Data were available for 303 patients who were enrolled in a placebo-controlled chemoprevention trial of low-dose 13-cis-retinoic acid to reduce the occurrence of SPTs.

METHODS

A Cox proportional hazards model and survival tree analysis were used to evaluate the association between specified genetic variations and the development of SPTs. The average number of bleomycin-induced chromatid breaks per cell was used to quantify mutagen sensitivity as an individual patient's degree of sensitivity to genotoxicity.

RESULTS

The GST-M1 null genotype was associated with an increased risk for any SPTs (hazard ratio [HR], 1.99; 95% confidence interval [95% CI], 1.11-3.56) and for tobacco-related SPTs (HR, 2.16; 95% CI, 1.01-4.62) after adjusting for covariates. The GST-T1 null genotype and bleomycin-induced chromatid breaks were not associated with a statistically significant increased risk for SPTs or tobacco-related SPTs after similar adjustment. Simultaneous nonnull status for both GST genotypes was associated with a decreased risk for any SPTs (HR, 0.52; 95% CI, 0.28-0.96) and tobacco-related SPTs (HR, 0.50; 95% CI, 0.22-1.11) compared with null status for GST-M1 accompanied by nonnull status for GST-T1.

CONCLUSIONS

An association was observed between the development of SPTs and the GST-M1 null genotype after successful treatment for early-stage head and neck squamous cell carcinoma. The GST-T1 null genotype and bleomycin-induced chromatid breaks were not associated with an increased risk, and no significant interactions were identified.

摘要

背景

本研究的目的是评估谷胱甘肽S-转移酶（GST）家族中2个基因的多态性以及诱变敏感性表型对先前诊断为早期头颈部鳞状细胞癌患者发生第二原发性肿瘤（SPT）风险的影响。有303例患者的数据，这些患者参与了一项低剂量13-顺式维甲酸的安慰剂对照化学预防试验，以降低SPT的发生率。

方法

采用Cox比例风险模型和生存树分析来评估特定基因变异与SPT发生之间的关联。将每细胞博来霉素诱导的染色单体断裂平均数用于量化诱变敏感性，作为个体患者对遗传毒性的敏感程度。

结果

在调整协变量后，GST-M1无效基因型与任何SPT（风险比[HR]，1.99；95%置信区间[95%CI]，1.11-3.56）以及与烟草相关的SPT（HR，2.16；95%CI，1.01-4.62）的风险增加相关。在类似调整后，GST-T1无效基因型和博来霉素诱导的染色单体断裂与SPT或与烟草相关的SPT的风险增加无统计学显著关联。与GST-M1无效状态伴GST-T1非无效状态相比，两种GST基因型同时为非无效状态与任何SPT（HR，0.52；95%CI，0.28-0.96）和与烟草相关的SPT（HR，0.50；95%CI，0.22-1.11）的风险降低相关。